**Author details**

generalizing them to the general practice an intriguing issue. There also seems a publication bias in reporting the trial results. Vascular surgery periodicals tend to note better results with

The modern medical treatment and optimized medical therapy (OMT) were not available at the time of some landmark trials like NASCET and ECST. There is a growing enthusiasm to test if OMT renders intervention unnecessary or only restricted to high risk patients. A new

**• European Carotid Surgery Trial-2 (ECST-2):** The trial will include patients with sympto‐ matic or asymptomatic moderate or severe carotid stenosis at low or intermediate risk of future stroke. The trial compares the risks and benefits of treatment by modern optimized medical management alone versus the addition of immediate carotid surgery (or stenting)

**• Asymptomatic Carotid Surgery Trial-2 (ACST-2):** To compare carotid endarterectomy with carotid artery stenting in the prevention of stroke in patients with asymptomatic carotid

**• Stent-protected angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy Trial-2 (SPACE-2):** A three-arm randomized-controlled clinical trial. The trial based on German speaking countries. The trial initially randomized patients with asymptomatic stenosis between carotid artery stenting vs. Carotid endarterectomy and recently the trial

**• Carotid Revascularization Endarterectomy versus Stenting Trial-2(CREST-2):** North American trial testing revascularization vs. contemporary medical management alone.

What we can infer from these trials that CEA has a lower stroke rate than CAS but CAS has a lower MI rate than CEA. If mortality, stroke and MI are mingled together as a single end-point, then both strategies are equivalent on the long-term. Advancing age is strongly against selecting CAS as the initial choice of revascularization. The results of either technique are critically dependent on the skills of the performing physician. Restenosis after CAS may be slightly more than restenosis after CEA but the severe, clinically significant restenosis is uncommon. In patients with concomitant coronary and carotid disease, stenting may have an

There remains a need for more trials assessing the future roles of medical management, carotid stenting, and carotid endarterectomy. Future trials should be designed with the assumption

modified to include third arm with optimized medical therapy (OMT) only.

CEA while cardiology journals tend to report superiority or non-inferiority of CAS.

**22. Ongoing trials and future directions**

120 Carotid Artery Disease - From Bench to Bedside and Beyond

to optimize medical management.

stenosis.

**23. Conclusion**

advantage over CEA.

set of trials called "Trials 2" are now developing and ongoing:

Hussien Heshmat Kassem1\*, Foad Abd-Allah2 and Mohammad Wasay3


### **References**


[9] Wholey, M.H., N. Al-Mubarek, and M.H. Wholey, Updated review of the global car‐ otid artery stent registry. Catheter Cardiovasc Interv, 2003. 60(2): p. 259-66.

[23] Arquizan, C., et al., Restenosis Is More Frequent After Carotid Stenting Than After

Update on Carotid Revascularization: Evidence from Large Clinical Trials

http://dx.doi.org/10.5772/57153

123

[24] Stingele, R., et al., Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis

[25] Bonati, L.H. and G. Fraedrich, Age Modifies the Relative Risk of Stenting versus En‐ darterectomy for Symptomatic Carotid Stenosis – A Pooled Analysis of EVA-3S, SPACE and ICSS. European Journal of Vascular and Endovascular Surgery, 2011.

[26] Ederle, J., et al., Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim

[27] Bonati, L.H., et al., New ischaemic brain lesions on MRI after stenting or endarterec‐ tomy for symptomatic carotid stenosis: a substudy of the International Carotid Stent‐

[28] Brott, T.G., et al., Stenting versus Endarterectomy for Treatment of Carotid-Artery

[29] Lal, B.K., et al., Restenosis after carotid artery stenting and endarterectomy: a secon‐ dary analysis of CREST, a randomised controlled trial. Lancet Neurol, 2012. 11(9): p.

[30] Cohen, D.J., et al., Health-related quality of life after carotid stenting versus carotid endarterectomy: results from CREST (Carotid Revascularization Endarterectomy

[31] Timaran, C.H., et al., Differential outcomes of carotid stenting and endarterectomy performed exclusively by vascular surgeons in the Carotid Revascularization Endar‐

[32] Clark, D.J., et al., Mechanisms and predictors of carotid artery stent restenosis: a seri‐ al intravascular ultrasound study. J Am Coll Cardiol, 2006. 47(12): p. 2390-6.

[33] Younis, G.A., et al., Predictors of carotid stent restenosis. Catheter Cardiovasc Interv,

[34] Wasser, K., et al., Clinical impact and predictors of carotid artery in-stent restenosis. J

[35] Sangiorgi, G., E. Romagnoli, and G. Biondi-Zoccai, Commentary: drug-eluting bal‐ loons for carotid in-stent restenosis: can this technology deliver the goods? J Endo‐

[36] Jost, D., et al., Surgical treatment of carotid in-stent-restenosis: novel strategy and

current management. Thorac Cardiovasc Surg, 2012. 60(8): p. 517-24.

terectomy versus Stenting Trial (CREST). J Vasc Surg, 2013. 57(2): p. 303-8.

Endarterectomy: The EVA-3S Study. Stroke, 2011. 42(4): p. 1015-1020.

of the SPACE study. The Lancet Neurology, 2008. 7(3): p. 216-222.

ing Study (ICSS). The Lancet Neurology, 2010. 9(4): p. 353-362.

Stenosis. New England Journal of Medicine, 2010. 363(1): p. 11-23.

Versus Stenting Trial). J Am Coll Cardiol, 2011. 58(15): p. 1557-65.

analysis of a randomised controlled trial. 2010.

41(2): p. 153-158.

755-63.

2007. 69(5): p. 673-82.

Neurol, 2012. 259(9): p. 1896-902.

vasc Ther, 2012. 19(6): p. 743-8.


[23] Arquizan, C., et al., Restenosis Is More Frequent After Carotid Stenting Than After Endarterectomy: The EVA-3S Study. Stroke, 2011. 42(4): p. 1015-1020.

[9] Wholey, M.H., N. Al-Mubarek, and M.H. Wholey, Updated review of the global car‐ otid artery stent registry. Catheter Cardiovasc Interv, 2003. 60(2): p. 259-66.

[10] Markus, H.S., et al., Improvement in cerebral hemodynamics after carotid angioplas‐

[11] Golledge, J., et al., Systematic comparison of the early outcome of angioplasty and endarterectomy for symptomatic carotid artery disease. Stroke, 2000. 31(6): p.

[12] Naylor, A.R., Randomized study of carotid angioplasty and stenting versus carotid endarterectomy: a stopped trial. Journal of Vascular Surgery, 1998. 28(2): p. 326-334.

[13] Hobson, R.W., 2nd, Regarding "Randomized study of carotid angioplasty and stent‐ ing versus carotid endarterectomy: a stopped trial". J Vasc Surg, 2000. 31(3): p. 622-4.

[14] Endovascular versus surgical treatment in patients with carotid stenosis in the Caro‐ tid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a rando‐

[15] Crawley, F., et al., Comparison of hemodynamic cerebral ischemia and microembolic signals detected during carotid endarterectomy and carotid angioplasty. Stroke,

[16] Mozes, G., et al., Carotid endarterectomy in sapphire-eligible high-risk patients: im‐ plications for selecting patients for carotid angioplasty and stenting. Journal of Vas‐

[17] Yadav, J.S., et al., Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk Patients. New England Journal of Medicine, 2004. 351(15): p. 1493-1501.

[18] Gurm, H.S., et al., Long-Term Results of Carotid Stenting versus Endarterectomy in High-Risk Patients. New England Journal of Medicine, 2008. 358(15): p. 1572-1579.

[19] Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS) phase I clinical trial: 1-year results. Journal of Vascular Surgery, 2005. 42(2): p.

[20] null, et al., 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

[21] Eckstein, H.-H., et al., Results of the Stent-Protected Angioplasty versus Carotid En‐ darterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multination‐ al, prospective, randomised trial. The Lancet Neurology, 2008. 7(10): p. 893-902.

[22] Mas, J.-L., et al., Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, mul‐

ticentre trial. The Lancet Neurology, 2008. 7(10): p. 885-892.

ty. Stroke, 1996. 27(4): p. 612-6.

122 Carotid Artery Disease - From Bench to Bedside and Beyond

1997. 28(12): p. 2460-4.

213-219.

mised trial. Lancet, 2001. 357(9270): p. 1729-37.

cular Surgery, 2004. 39(5): p. 958-965.

Lancet, 2006. 368(9543): p. 1239-1247.

1439-43.


[37] Raithel, D., Recurrent carotid disease: optimum technique for redo surgery. J Endo‐ vasc Surg, 1996. 3(1): p. 69-75.

**Chapter 6**

**Oxidised Low Density Lipoprotein (LDL) Modification**

Carotid artery stenosis due to atherosclerosis is a major complication of hyperlipidemia, diabetes mellitus and hypertension. Moreover, the extent of carotid intima media thickness is

The effect of cholesterol in the process of atheromatosis is now well established. High levels of total cholesterol, as well as of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), lipoprotein a (Lp-α), and triglycerides, coupled with decreased levels of high-density lipoprotein (HDL) are responsible for the creation of atheromatous plaques [1-3]. Of the above factors, LDL cholesterol, and especially the oxidized LDL is considered as the most important contributor of atheromatosis [4].

**1.** In the first stage, LDL cholesterol enters the vessel wall, binds to gluxosaminoglucanes, which are part of the extracellulat matrix of the intima. This binding is facilitated by apolipoprotein B-100 (ApoΒ–100). The accumulation of LDL in the vessel wall contributes to the formation of fatty strikes. Following LDL adhesion in the vessel wall, it undergoes oxidation by free radicals produced locally, the molecule is altered and chemokines are produced by adjacent vessel wall cells, such as MCP – 1, together with growth factors, which are responsible for the accumulation of monocytes and macrophages. The latter,

> © 2014 Skopelitis et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

a measure of atheromatosis and therefore of cardiovascular disease (CVD).

The atheromatous process is completed in the following three stages:

**with Statin Therapy is Associated with Reduction in**

**Carotid Stenosis**

http://dx.doi.org/10.5772/57188

**1. Introduction**

Elias Skopelitis, Dimitrios Levisianou, Helen Lydataki and Sofoklis Kougialis

Additional information is available at the end of the chapter

**1.1. Carotid stenosis and atheromatous process**

